Ultra long pulsed dye laser device for treatment of ectatic vessels and method therefor

ABSTRACT

A long pulsed dye laser device for selective photothermolysis comprises at least two pulsed dye lasers, such as flash lamp excited dye lasers, each generating corresponding pulsed laser beams successively in time. These laser can be coordinated by a synchronizer that sequentially triggers the lasers. A combining network merges the pulse laser beams into a combined beam and a delivery system conveys the combined pulse laser beam to a patient. An example of a delivery device is a single optical fiber. This invention enables production of the necessary pulse widths, on the order of 2 msec, which can not be achieved by individual dye lasers, generally lower than 0.8 msec. Also disclosed is a selective photothermolysis method. This method comprises irradiating a tissue section of a patient with a pulsed laser beam having a changing color across a time period of the pulse. This pulse color is selected to maximize absorption in a target tissue of a patient in response to heating caused by a preceding portion of the pulse.

RELATED APPLICATION

This application is a Continuation of U.S. Ser. No. 08/695,661, filedAug. 8, 1996, now U.S. Pat. No. 5,746,735 which is aFile-Wrapper-Continuation of Ser. No. 08/329,195, filed Oct. 26, 1994,now abandoned, the entire teachings of which are incorporated herein byreference.

BACKGROUND OF THE INVENTION

Vascular lesions comprising enlarged or ectatic blood vessels have beensuccessfully treated with lasers for many years. In the process, calledselective photothermolysis (SP), the lesion is irradiated with laserlight. The wavelength or color of the laser light is chosen so that itsenergy is preferentially absorbed into the lesion, the target tissue.Most commonly in the context of vascular lesions, such as portwinestains for example, hemoglobin of red blood cells within the ectaticblood vessels serves as the chromophore. Ideally, these cells absorb theenergy of the laser light and transfer this energy to the surroundingvessels as heat. If this occurs quickly and with enough energy, thesurrounding vessels reach a temperature to denature their proteins,which leads to their ultimate destruction. The fluence to reach thedenaturation of the vessels is calculated to be that necessary to raisethe temperature of the targeted volume within the vessel to about 70° C.before a significant portion of the absorbed laser energy can diffuseout of the vessel.

Flash lamp excited dye lasers meet the wavelength constraints requiredfor selectivity. These lasers are readily tunable to generate pulsedlaser light in a range around 580 nm. The greatest disparities betweenthe absorption of hemoglobin and melanin, the principle pigment in theskin, exist in this range.

Wavelength aside, the intensity and pulse width of the laser light mustalso be optimized in order to maximize selectivity. Proper pulseduration and intensity are important to attain temperatures necessary todenature the vessel's protein without heating too quickly the red bloodcells. Boiling and vaporization are desirably avoided since they lead tomechanical, rather than chemical, damage, which can increase injury andhemorrhage in tissue surrounding the lesion. These constraints suggestthat the pulse duration should be longer with a correspondingly lowerintensity to avoid vaporization. Because of thermal diffusivity, energyfrom the laser light pulse must be deposited quickly, however, tominimize heat dissipation into the surrounding tissue. The situationbecomes more complex if the chromophore is the blood cell hemoglobinwithin the lesion blood vessels, since the vessels are an order ofmagnitude larger than the blood cells. Radiation must be added at lowintensities so as to not vaporize the small cells, yet long enough toheat the blood vessels by thermal diffusion to the point of denaturationand then terminated before tissue surrounding the blood vessels isdamaged.

Theory suggests that the length of the laser light pulse should be onthe order of milliseconds, especially for adult patents havingcharacteristically thicker and larger blood vessels. Commerciallyavailable dye lasers, however, are generally limited in the pulsedurations to approximately 0.5 msec.

A number of attempts have been made to increase the pulse length of dyelasers. One approach is disclosed in U.S. Pat. No. 4,829,262 granted toone of the present inventors. This invention was directed to overcomingthermal distortion in the lasing medium, which leads to loss of theresonating modes. Special resonator optics were proposed that would beless sensitive to opto-acoustic perturbations. Other attempts toincrease pulse length have been made by implementing planar waveguidelasers. See Burlmacchi, et al., “High Energy Planar Self Guiding DyeLaser,” Optics Communication, 11(109) (1974).

SUMMARY OF THE INVENTION

Recent research suggests that special resonators do not prolong pulseduration longer than standard resonator designs. This realization leadsto the conclusion that there must be another reason for the quenching ofthe lasing action than thermal distortion. Subsequent studies on longpulse flash lamp excited dye lasers show that it is nearly impossible toextract pulses from a flash lamp excited dye laser more than onemillisecond long and still meet the energy requirements of an outputgreater than one hundred millijoules needed for SP.

It seems that induced absorption could be a factor in quenching thelasing action. Although transient absorption can be induced, the largestcontribution is considered to be permanent transformation in the dye toa light absorbing specie. The dye concentration is set for uniformabsorption of pump light across the short dimension of the dye cell,approximately 4 mm. The concentration optimizes at about 7×10⁻⁵M of dyesolution. Meanwhile, the laser length is 600 mm or 150 times longer thanthe dye cell diameter. A 1/e transmission loss along the gain lengthwould overcome any gain in the laser. The concentration of absorbingspecie need only be minuscule, on the order of 3×10⁻⁷ M to stop anygain. This small concentration of absorbers can be readily generatedduring the excitation pulse.

In light of the fact that research seems to establish that a dye lasercan not produce the necessary pulse widths, the present invention isbased upon the recognition that the required pulse widths could beachieved by implementing multiple dye lasers and time multiplexing theiroutput beams. For example, if the required pulse width is on the orderof two msec, the pulse laser beams from two lasers, each beingapproximately 0.8 msec long could be multiplexed in time and combined toeffectively meet this width specification.

Moreover, the implementation of time multiplexed multi-colored pulselaser beams allows the dynamic tracking of the absorption spectra of thechromophore, hemoglobin for example, as it is heated. With temporalmultiplexing, lasers of different colors can be used to optimize theselectivity in response to the predicted temperature of the targettissue.

As a result, in general according to one aspect, the invention featuresa long pulsed laser device for selective photothermolysis. This devicecomprises at least two pulsed lasers, generating successive laserpulses. The laser can be coordinated by a synchronizer that sequentiallytriggers the laser. A combining network merges the pulse laser beamsinto a combined bean and a delivery system conveys the combined laserbeam to a patient. Such a combined beam may have an energy of 100millijoules and a pulse duration from 1 to 10 msec.

In general, according to another aspect, the invention features a methodfor generating a long effective laser pulse for a selectivephotothermolysis therapy. This method comprises successively triggeringat least two pulse lasers to generate pulsed laser beams. These beamsare then combined into a combined beam having all effective pulse widthequal to a combination of the pulsed laser beams. Finally, the combinedbeam is delivered to a patient thought a delivery system.

In general, according to another aspect, the invention features aselective photothermolysis method. This method comprises irradiating atissue section of a patient with a pulsed laser beam having a changingcolor across a time period of the pulse. This color is selected tomaximize absorption in a target tissue of a patient in response toheating caused by a preceding portion of the pulse.

The above and other features of the invention including various noveldetails of construction and combinations of parts, and other advantages,will now be more particularly described with reference to theaccompanying drawings and pointed out in the claims. It will beunderstood that the particular method and device embodying the inventionis shown by way of illustration and not as a limitation of theinvention. The principles and features of this invention may be employedand various and numerous embodiments without the departing from thescope of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

In the accompanying drawings, like reference characters refer to thesame parts throughout the different views. The drawings are notnecessarily to scale. Emphasis is instead placed upon illustrating theprinciples of the invention. Of the drawings:

FIG. 1 is a schematic view of a first embodiment of an ultra-long pulseddye laser device of the present invention;

FIG. 2 is a graph of output beam intensity as a function of time for thefirst embodiment dye laser device of FIG. 1;

FIG. 3 is a schematic view of a second embodiment of a pulsed dye laserdevice of the present invention;

FIG. 4 is a schematic view of a third embodiment of the pulsed dye laserdevice of the present invention, combining the output of four lasers;

FIG. 5 is a graph of output beam intensity as a function of time for thethird embodiment dye laser device of FIG. 4;

FIG. 6 is a schematic view of a fourth embodiment of the pulsed dyelaser device of the present invention; and

FIG. 7 is a schematic view of a fifth embodiment of the pulsed dye laserdevice of the present invention.

DETAILED DESCRIPTION OF THE DRAWINGS

Turning now to the drawings, a first embodiment 100 of a dye laserdevice, constructed according to the principles of the presentinvention, is illustrated in FIG. 1. Generally, two pulse lasers 110,120 are commonly controlled to generate two pulsed laser beams b₁₁₀,b₁₂₀, one being delayed in time with respect to the other. These beamsare then merged into a single beam b₁₄₀ by a combining network, see 140,142. This merged beam b₁₄₀ is conveyed to a targeted region of thepatient, such as that containing a cutaneous portwine stain, by adelivery system, see 160.

In more detail, a synchronizer 105 generates two trigger signalsSync₁₁₀, Sync₁₂₀, with Sync₁₂₀ being delayed in time by approximately1.3 msec with respect to Sync₁₁₀. In response to their correspondingtrigger signals, the lasers 110, 120 generate pulsed laser beams b₁₁₀,b₁₂₀. In the preferred embodiment, the lasers are long pulse flashlampexcited dye lasers.

Pulse laser beam b₁₂₀ is redirected by a fold mirror 142 to spatiallyconverge with beam b₁₁₀ at a polarizer 140. The pulsed laser beams b₁₁₀,b₁₂₀ are generated by their corresponding lasers 110, 120 to haveorthogonal polarizations with respect to each other. This can beachieved by filtration at the output of the lasers 110, 120 usingorthogonally oriented polarizing filters or by appropriate design of thelasers' resonant cavities. The polarizer 140 is designed and configuredsuch that it permits the transmission of light having the polarizationof beam b₁₁₀ but reflects light having a polarization of beam b₁₂₀. As aresult, the pulsed laser beams are combined by the combining network140, 142 into merged beam b₁₄₀.

This merged beam is then coupled into a single optical fiber 160 servingas the preferred delivery system. Alternatively, a fiber optic bundlemay be used. Beam b₁₄₀ appears as an output beam b_(out) from the fiber160 and is applied to the tissue 10 of a patient.

As illustrated in FIG. 2, the merged and output beams b_(140,out)comprise two light pulses b₁₁₀, b₁₂₀ which are attributable respectivelyto the lasers 110, 120. As a result, the effective pulse width Wgenerated by the first embodiment system 100 exceeds 2 msec even thoughthe maximum obtainable pulse width from currently available dye lasersdoes not exceed 0.8 msec, and is closer to 0.5 msec for those availablecommercially. More specifically, the effective pulse width of the mergedbeam b₁₄₀ is equal to the pulse widths of the two pulsed laser beams T₁plus T₂ in addition to an inter-pulse delay d₁. It should also berecognized that the time period T₁ plus d₁ corresponds to the time delaybetween the trigger signals Sync₁₁₀ and Sync₁₂₀ on the assumption thatthe lasers 110, 120 have the same latency to beam generation. As aresult, the first embodiment enables the production of longer effectivelaser pulses. This feature enables the more effective treatment ofthicker vascular lesions associated with, for example, portwine stainsin adults in which the lower limit optimum pulse duration is about onemillisecond long to treat vessels 100 microns or larger in diameter, asis. characteristic of this age group. Consequently, the thermaldiffusion time of the target tissue, in this case, benign cutaneousvascular lesions, can be more accurately matched to optimize treatmentand minimize damage to surrounding tissue.

Referring to FIG. 3, a second embodiment 200 of the pulsed dye laserdevice is shown in which a combining network 240, 242 includes adichroic mirror. As discussed in reference to FIGS. 1 and 2 inconnection with the first embodiment 100, a synchronizer 205 generatestwo trigger signals to lasers 210 and 220. Since the trigger signalprovided to laser 220 is delayed in time, pulse laser beam b₂₂₀ isdelayed in time with respect to b₂₁₀. In contrast to the firstembodiment 100, these laser beams b₂₁₀, b₂₂₀ are not orthogonallypolarized but are comprised of different colored light. The combiningnetwork comprises a fold mirror 242 and a dichroic mirror 240. The foldmirror 242 redirects beam b₂₂₀ to converge spatially with beam b₂₁₀ atthe dichroic mirror 240. This dichroic mirror 240 is constructed totransmit wavelengths characteristic of the beam b₂₁₀ but reflect lighthaving a wavelength of beam b₂₂₀. As a result, a merged beam b₂₄₀ isgenerated which is comprised of a leading pulse resulting from thepulsed laser beam b₂₁₀ and a second delayed pulse which is resultingfrom the pulse b₂₂₀.

Ideally, the wavelengths or colors of the two pulsed beams b₂₁₀ and b₂₂₀are optimized to maximize the wavelength dependent selectivity of the SPprocess. That is, in SP, the wavelength of the pulsed laser beam isselected to maximize the degree to which the beam is absorbed by thetarget tissue and minimize absorption in the surrounding tissue. Thesewavelengths are found in the range of 540-630 nm. The optimumwavelength, however, in many situations is dependent on the previouspulse. That is, the absorption spectra for hemoglobin becomes broaderand more broadband as the hemoglobin is denatured due to precedingportions of the pulse. The color of merged beam b₂₄₀ is selected todynamically match this change. The colors of the lasers 210, 220 can beformulated by selecting the appropriate dye recipe or intra-cavitytreating elements such as etalons, bifringent filters, prisms orgradings. Thus, the present invention enables the achievement of higherlevels of selectivity by matching the time dependent color of the mergedpulse b₂₄₀ to the absorption characteristics as they change during theirradiation of the target tissue.

The first and second embodiments 100, 200 enable the generation ofeffective pulse lengths on the order of 200% greater than thatachievable by single dye lasers. Cutaneous lesions comprising thickerwalled ectatic vessels in some cases require even longer effective pulselengths to optimize selectivity toward the target tissue. That is,effective pulse widths on the order of 2 msec, which are achievable asshown in FIG. 2, may still not be optimum. Many patients need energiesgreater than 100 millijoules with pulse durations of 1 to 10 msec. Thethird embodiment illustrated in FIG. 4 enables the combination of fourpulse laser beams into a single output beam b_(out). In this embodiment,a synchronizer 305 presents four trigger signals progressively delayedin time to four lasers 310, 314, 318, 320. As a result, four pulse laserbeams b₃₁₀, b₃₁₄, b₃₁₈, b₃₂₀ are correspondingly generated.

The net spatial lateral distance between each of these beams isminimized by reflecting each of the outer beams b₃₁₀ and b₃₂₀ off adifferent pair of fold mirrors f₁ and f₂ in the case of beam b₃₁₀ andmirrors f₃ and f₄ in the case of beam b₃₂₀. All four laser pulse beamsare then coupled into a single optical fiber 360 by focusing lens 342.

Preferably, the fiber 360 is large caliber between 0.4 and 1.5 mm andhas a large acceptance numerical aperture of 0.3 to 0.42.

As illustrated in FIG. 5, the synchronizer 305 triggers each of theselasers 310, 314, 318, and 320 to generate the corresponding pulsed beamsb₃₁₀, b_(3l4), b₃₁₈, and b₃₂₀ to be evenly delayed in time so that theoutput beam bout will have an effective pulse width of approximately 4.5msec.

One potential modification of the third embodiment is to essentiallyconnect fold mirrors f₁ and f₄ with an fold mirrors situated concentricto the main axis that would extend perpendicularly out of the page inFIG. 4 and be concentric with the lens 342. This change would enable acircular array of lasers to generate beams which could be coupled intothe fiber optic cable 360 enabling even longer effective pulse widths.

FIG. 6 shows a fourth embodiment of the present invention for alsocoupling the outputs of four lasers 410; 414, 418, 420 into a singleoptical fiber 460. In this embodiment, each of the lasers 410-420 isagain controlled by a synchronizer 405 to successively generate in timethe pulses. These pulses are individually coupled into separate fiberoptic transfer cables 440, 442, 444, and 446 by focusing lens 1 ₁-1 ₄.These transfer cables 440-446 are spatially brought together intoessentially a single bundle of four parallel fibers at a proximal end447. This enables a single lens 448 to couple the outputs of each ofthese fibers 440-446 into fiber 460 of the delivery system.

Finally, FIG. 7 shows a fifth embodiment of the present invention. Thisembodiment is somewhat related to a combination of the first and secondembodiments of FIGS. 1 and 3 in that it incorporates both a polarizer540 and dichroic mirrors 544, 546. But, this fifth embodiment couplesthe time delay outputs of a total of four lasers 510, 514, 518, and 520.More specifically, a first pair of lasers 518, 520 generate a pair ofoutput beams b₅₁₈ and b₅₂₀ that have different colors but the samepolarization. The dichroic mirror 546 is selected such that it reflectslight having a color of beam b₅₁₀ but passes light having a color ofbeam b₅₁₄. As a result, the beams are spatially merged into a singlebeam b₅₄₆. In a similar vein, a second pair of lasers 518, 520 producebeams b₅₁₈ and b₅₂₀ that are merged into a single beam b₅₄₄ by dichroicmirror 544. Beams b₅₁₈ and b₅₂₀, however, have a polarization that isperpendicular to beams b₅₁₀ and b₅₁₄. A polarizer 540 merges beams b₅₄₄and b₅₄₆ into single combined beam b₅₄₀, which is conveyed to thepatient by optical fiber 560. This is accomplished by virtue of the factthat polarizer 540 is oriented such that light having the polarizationof beam b₅₄₆ is transmitted but light having the orthogonal polarizationof beam b₅₄₄ is reflected. Thus, a single beam b₅₄₀ is generated whichcomprises two colors and pulses from four lasers. It will be understoodthat the same outcome could be realized by reversing the configurationusing two polarizers, and a single dichroic mirror, and rearranging thelasers 510-520.

While this invention has been particularly shown and describe withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the spirit and scope of theinvention as defined by the appended claims.

What is claimed is:
 1. A method for generating a long effective laserpulse for selective photothermolysis, therapy comprising: generatingmultiple laser pulses; generating a combined pulse from the multiplepulses, selecting a color of a subsequent one of the laser pulses in thecombined pulse to maximize absorption in a target tissue of a patient inresponse to heating caused by a preceding one of the laser pulses in thecombined laser pulse, the combined pulse having an effective pulse widthgreater than the laser pulses individually; and delivering the combinedpulse to a patient through a delivery system.